HEV Seroprevalence, Serum and Feces HEV RNA positivity in Post-Liver Transplant Patients During 1-year Follow-up Period

Abstract

Introduction: Hepatitis E virus (HEV) has emerged as an important infectious disease in immunocompromised patients, especially those who are post-liver transplanted (LT). Reported HEV seroprevalence rates in general populations of Europe and the United States are 5-12% and 19%, respectively. Reported HEV RNA detection rates are remarkably lower, however, being 1.4% in Europe and 0.12% in Japan. We evaluated the HEV seroprevalence and RNA detection in post-LT patients to evaluate the hypothesis that HEV may pose potential subclinical risk in this particular immunocompromised patient population. Method: 106 post-LT patients were enrolled and provided blood and feces samples. All patients were tested for HEV seroprevalence. After exclusion of acute/chronic HEV cases (n=3) and other unavailable cases (n=13), 91 post-LT patients were investigated for HEV serology (IgG and IgM) and HEV RNA detection (serum and feces) every 4 months during 1-year follow-up period. All patient samples were kept in -70C storage. HEV RNA in serum and feces were detected by real-time (in-house) RT-PCR technique (lowest level of detection=10 IU/mL). Demographic and clinical data were retrieved from the medical records for descriptive statistical analysis. Result: The 106 post-LT patients had an HEV seroprevalence of 53.8%. After exclusion of the unavailable cases, 91 post-LT patients were prospectively investigated. HEV seropositive group was 50.5%, while the seronegative group was 49.5%. Baseline characteristics between two groups were not different. The serum and feces HEV RNA detection at baseline in seropositive group were 5/46 (21%) and 1/46 (2%), respectively. In seronegative group, the serum and feces HEV RNA detection were 2/45 (4.5%) and 3/45 (6.7%), respectively. Due to unprecedently high in proportion of patients with positive serum HEV RNA in both groups at the 4th visit, we decided to report our prospective result of the 8-month follow-up period. In seropositive group, serum and feces HEV RNA were detected in 11/46 (24%), 3/46 (6.5%), respectively. In seronegative group, serum and feces HEV RNA were detected in 9/45 (20%), 4/45 (8.8%), respectively. During 8-month period, 8 out of 14 and 8 out of 13 more cases of positive HEV in serum or feces in patients with and without IgG (+) were newly discovered, respectively. 2 out of 27 patients with positive serum or feces HEV RNA had abnormal liver function tests and one case was proved to be from anastomosis stricture with intrahepatic stone which was relieved after underwent ERCP. Conclusion: Thailand has high prevalence of HEV seroprevalence in post LT patients. Post-LT patients could have subclinical HEV infection without obvious clinical clues. Without HEV RNA assays, active HEV infection could be missed even in HEV IgG seronegative patients. Feces HEV RNA detection adds on benefit of the diagnostic yield. However, clinical significance of these silence detection remains to be elucidated